Cross-talk Between Nitrate-Nitrite-NO and NO Synthase Pathways in Control of Vascular NO Homeostasis
2015 (English)In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 23, no 4, 295-306 p.Article in journal (Refereed) PublishedText
Aims: Inorganic nitrate and nitrite from endogenous and dietary sources have emerged as alternative substrates for nitric oxide (NO) formation in addition to the classic L-arginine NO synthase (NOS)-dependent pathway. Here, we investigated a potential cross-talk between these two pathways in the regulation of vascular function. Results: Long-term dietary supplementation with sodium nitrate (0.1 and 1mmol kg(-1) day(-1)) in rats caused a reversible dose-dependent reduction in phosphorylated endothelial NOS (eNOS) (Ser1177) in aorta and a concomitant increase in phosphorylation at Thr495. Moreover, eNOS-dependent vascular responses were attenuated in vessels harvested from nitrate-treated mice or when nitrite was acutely added to control vessels. The citrulline-to-arginine ratio in plasma, as a measure of eNOS activity, was reduced in nitrate-treated rodents. Telemetry measurements revealed that a low dietary nitrate dose reduced blood pressure, whereas a higher dose was associated with a paradoxical elevation. Finally, plasma cyclic guanosine monophosphate increased in mice that were treated with a low dietary nitrate dose and decreased with a higher dose. Innovation and Conclusions: These results demonstrate the existence of a cross-talk between the nitrate-nitrite-NO pathway and the NOS-dependent pathway in control of vascular NO homeostasis. Antioxid. Redox Signal. 23, 295-306.
Place, publisher, year, edition, pages
2015. Vol. 23, no 4, 295-306 p.
Endocrinology and Diabetes Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
IdentifiersURN: urn:nbn:se:uu:diva-268717DOI: 10.1089/ars.2013.5481ISI: 000363895200002PubMedID: 24224525OAI: oai:DiVA.org:uu-268717DiVA: diva2:878797
FunderSwedish Research Council, K2012-99X-21971-01-3VINNOVASwedish Heart Lung Foundation, 20110589EU, FP7, Seventh Framework ProgrammeWenner-Gren FoundationsSwedish Society for Medical Research (SSMF)